Biosynthesis of saponin defensive compounds in sea cucumbers

Abstract

Soft-bodied slow-moving sea creatures such as sea stars and sea cucumbers lack an adaptive immune system and have instead evolved the ability to make specialized protective chemicals (glycosylated steroids and triterpenes) as part of their innate immune system. This raises the intriguing question of how these biosynthetic pathways have evolved. Sea star saponins are steroidal, while those of the sea cucumber are triterpenoid. Sterol biosynthesis in animals involves cyclization of 2,3-oxidosqualene to lanosterol by the oxidosqualene cyclase (OSC) enzyme lanosterol synthase (LSS). Here we show that sea cucumbers lack LSS and instead have two divergent OSCs that produce triterpene saponins and that are likely to have evolved from an ancestral LSS by gene duplication and neofunctionalization. We further show that sea cucumbers make alternate sterols that confer protection against self-poisoning by their own saponins. Collectively, these events have enabled sea cucumbers to evolve the ability to produce saponins and saponin-resistant sterols concomitantly.

Discovering a uniform functional trade-off of the CBC-type 2,3-oxidosqualene cyclases and deciphering its chemical logic

“…6A and figs. S10 and S11), the functional plasticity of the F in other OSCs was further investigated, including It OSC3 from Iris tectorum Maxim ( 5 ), Sg CBQ from Siraitia grosvenorii ( 13 ), Aj PS from Apostichopus japonicus ( 14 , 15 ), and ERG7 from Saccharomyces cerevisiae ( 16 ), as all these OSCs have F at the same site as F726 in Ao CAS.…”

Bioactive Cembranoids from the Coral Sarcophyton trocheliophorum of Ximao Island

“…However, the biosynthesis of the diverse and bioactive cembranoids remains elusive. Recent reports on the identifications of terpene synthases, including cembrane synthase, from marine invertebrates, − have proved that marine animals contain functional genes responsible for the biosynthesis of bioactive terpenoids, which are likely used as a “chemical weapon” against predators. , These previous reports have opened the door to elucidate the biosynthesis of bioactive, soft coral-derived cembranoids. Because these compounds are often found in extremely low yield, understanding their biosynthetic pathways could allow for their overproduction in genetically engineered systems to assist downstream drug development of cembranoids and to assist efforts in chemical ecology to protect coral ecosystems.…”

Marine natural products

“…Sea cucumbers lack this enzyme, relying instead upon two oxidosqualene cyclase enzymes that appear to have evolved from an ancestral lanosterol synthase. 621 With the common occurrence of steroidal glycosides in sea cucumbers, and the knowledge that saponins act as membrane disruptors, the authors noted the ability of the marine organisms to produce larger quantities of lathosterol and related sterols that appear to confer protection from saponin self-poisoning. Further biological evaluation of sea cucumber metabolites has identified the simple fatty acid decanoic acid as being active in a number of Parkinson's disease related models and assays, 622 desulfated echinoside A has much reduced haemolytic activities and can still act to lower lipid levels in vitro and in vivo , 623 and the saponin stichloroside C2 is cytotoxic towards triple-negative breast cancer cells via mechanisms that include inhibition of epithelial–mesenchymal transition and the induction of apoptosis via the MAPK signalling pathway.…”